The degree of cancer progression or enlargement is described as early cancer, advanced cancer, and terminal cancer. Among them, early cancer is generally considered as “a degree of cancer progression in which the tumor is small, shows few metastases, and can be cured permanently or the cancer can be subdued for a long time through treatment”.
Early cancer is basically symptomless. Therefore, symptomless subjects are the targets who are tested when trying to nearly completely detect early cancer. Tests targeting a broad range of symptomless subjects to find patients affected by a particular disease, or to narrow down the subjects to those requiring advanced secondary tests, are generally called screening. Generally, in screening, the number of test subjects is extremely large. In order to test many subjects, the screening should first and foremost be convenient and economical. Although testing for tumor markers is a favorable testing method with little invasion of patients, currently, detection of early cancer by measuring tumor markers is considered impossible.
Midkine (hereinafter, referred to as “MK”) is a proliferation and differentiation factor that was discovered as a retinoic acid-responsive gene product, and is a 13-kDa polypeptide rich in basic amino acids and cysteines (Kadomatsu, K. et al.: Biochem. Biophys. Res. Commun., 151: 1312–1318; Tomomura, M. et al.: J. Biol. Chem., 265: 10765–10770, 1990). The fact that the MK level is elevated in various malignant tumors compared to the surrounding normal tissues, suggests that MK plays an important role in carcinogenesis. Consequently, diagnosis of cancer by Northern blotting using MK gene as a probe (Unexamined Published Japanese Patent Application No. (JP-A) Hei 6-113898) and a diagnostic agent for cancer containing anti-MK protein antibody (JP-A Hei 6-172218) have been suggested. However, these published patent applications do not describe nor suggest that MK genes or MK proteins are useful in early cancer detection. Thereafter, Ye et al. have reported that MK expression is elevated in pre-cancerous tissues at adenoma stages of human colorectal cancer (Ye C. et al.: Br. J Cancer., 79: 179–183, 1999). However, there is no description or suggestion in this report regarding early cancer detection.
Therefore, the discovery of tumor markers that may be detected from early cancer conditions and the development of tests for detecting such markers have been anticipated.